In a method of operating an internal combustion engine which has at least two cylinder banks that can be controlled separately as a function of a desired load, wherein a desired pressure in the intake pipe of the internal combustion engine is determined and set by means of an air supply device for supplying combustion air to the cylinders of the internal combustion engine, at least one engine-related characteristic value which affects the behavior of the internal combustion engine is determined for each cylinder bank, and, in the event of a difference between the characteristic values of the cylinder banks, at least one cylinder bank is manipulated in such a way that the average value of the considered characteristic quantity corresponds to a desired average value in order to reduce the thermodynamic and mechanical loading of the internal combustion engine with bank-selective operating mode.